Melanoma is an increasingly frequent cutaneous malignancy with a familial predisposition evident in about ten percent of cases. The familial dysplastic nevus syndrome (FDNS) is a dominantly inherited disorder characterized by clinically and histologically distinct melanocytic lesions which predispose affected individuals to melanoma. Prior efforts to identify the gene(s) responsible for this syndrome have generated conflicting data. We propose to define the linkage relationships between the FDNS phenotype and several candidate genes which are expressed in skin, in an effort to identify the locus or loci which may harbor the primary mutation(s) in this disorder. Large pedigrees with FDNS have been ascertained, and they will be recruited to participate in the study. Novel DNA polymorphisms will be developed, and together with existing polymorphisms, genotypes will be determined for epidermal growth factors, their receptors, and other candidate loci by means of Southern blotting and PCR-based assays. Linkage analysis will be carried out using LIPED and related computer programs. Establishment of significant linkage to one or more loci will form the basis of characterization of mutations responsible for the progression of nevi to melanoma in these families.